Baş Boyun Radyoterapilerine Bağlı Oral Mukozitler
Özet
Baş boyun radyoterapisi alan hastaların %80-95'inde görülen oral mukozit, ağız boşluğu ve farenks mukozasında inflamasyon ile ülserasyonla karakterize, hastaların genel yaşam kalitesini oldukça belirgin şekilde düşüren en sık erken dönem yan etkilerden biridir. Genellikle radyasyon tedavisinin ikinci haftasında başlayan ve altıncı haftaya kadar şiddeti gittikçe artış gösteren bu karmaşık patoloji; doku hasarının başlaması, inflamasyonun aktivasyonu, sinyallerin büyümesi (amplifikasyonu), klinik olarak en kritik evre olan ülserasyon ve son olarak doku bütünlüğünün yeniden kazanıldığı iyileşme olmak üzere beş aşamalı bir patojenik süreçte gelişmektedir. Yüksek radyasyon dozları, eş zamanlı kemoradyoterapi uygulamaları, ileri yaş, düşük vücut kitle indeksi, kötü ağız hijyeni ve bazı genetik polimorfizmler ağır mukozit gelişimi için en önemli risk faktörlerini oluşturmaktadır. Ağır vakalarda ortaya çıkan ciddi beslenme bozuklukları; enteral-parenteral beslenme ve gastrostomi ihtiyaçlarını doğururken, hastaların yaklaşık %11'inde radyoterapi tedavisine bir süre ara verilmesini zorunlu kılmakta, sekonder enfeksiyonlar ve hastane yatışları sebebiyle de tedavi maliyetlerini doğrudan artırmaktadır. Dünya Sağlık Örgütü (WHO) ve NCI gibi sistemlerle sınıflandırılan mukozitin yönetiminde, güncel MASCC/ISOO kılavuzları doğrultusunda hasta eğitimi, temel ağız bakımı protokolleri, benzidamin gargaraları, palifermin kullanımı, fotobiyomodülasyon (düşük dozlu lazer tedavisi), kriyoterapi kombinasyonları ve doğal bir destek olarak balın kullanımı tavsiye edilmektedir. Sonuç olarak, onkolojik tedavilerin kesintisiz sürdürülebilmesi ve klinik başarının optimize edilmesi adına mukozitin etkin şekilde önlenmesi kritik bir öneme sahiptir.
Oral mucositis, characterized by severe inflammation and ulceration of the oral cavity and pharyngeal mucosa, represents a major early-stage complication affecting approximately 80-95% of patients undergoing head and neck radiotherapy, deeply compromising their overall quality of life. Typically initiating during the second week of radiation treatment and progressively intensifying through the sixth week, its complex pathogenesis evolves through five biological phases: initiation of tissue damage, activation of inflammation, signal amplification, symptomatic ulceration, and epithelial healing. High radiation doses, concomitant chemoradiotherapy regimens, advanced age, low body mass index, poor oral hygiene, and distinct genetic polymorphisms constitute the primary risk factors for severe mucositis development. Severe manifestations induce profound nutritional deficits, necessitating enteral or parenteral nutrition and gastrostomy, while compelling treatment interruption in up to 11% of affected individuals and escalating overall healthcare costs due to secondary infections and extended hospitalizations. Standardized through grading scales established by the WHO and NCI, management following the latest MASCC/ISOO guidelines highly recommends patient education, basic oral care protocols, benzydamine rinses, palifermin administration, photobiomodulation via low-level laser therapy, cryotherapy, and honey as an evidence-based natural intervention. Ultimately, proactive prevention and structured treatment of oral mucositis remain absolutely paramount in head and neck oncology to maintain uninterrupted therapeutic regimens and minimize severe clinical burdens.
Referanslar
Stewart FA, Akleyev AV, Hauer-Jensen M, et al. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context. Ann ICRP. 2012; 41(1-2):1-322.
Shiboski CH, Hodgson TA, Ship JA, Schiodt M. Managementof salivary hypofunction during and after radiotherapy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2007;103(Suppl):S66 e1-19
De Castro G, Federico MHH. Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients. Current opinion in oncology. 2006;18(3):266-70.
Palmieri M, Sarmento DJS, Falcão AP, et al. Frequency and Evolution of Acute Oral Complications in Patients Undergoing Radiochemotherapy Treatment for Head and Neck Squamous Cell Carcinoma. Ear, Nose & Throat Journal.2021;100(5 suppl):449–55.
Sonis ST. Oral Mucositis in Head and Neck Cancer: Risk,Biology, and Management. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology Educational Book; 2013;(33):e236–40.
Caudell JJ, Ward MC, Riaz N, et al Volume, Dose, and Fractionation Considerations for IMRT-based Reirradiation in Head and Neck Cancer: A Multi-institution Analysis. International Journal of Radiation Oncology-Biology-Physics. 2018;100(3):606-617.
Lalla, R.V, Saunders, D.P, Peterson, D.E. Chemotherapy or radiation-induced oral mucositis. Dent. Clin. N. Am. 2014;58: 341–49
Engin K, Erişen L. (2003).Baş Boyun Kanserleri(1. Bs).Bursa: Nobel Tıp Kitabevi
Gökcan MK. (2018). Orofarenks ve Hipofarenks Hastalıkları. Metin Önerci (Ed.), Kulak Burun Boğaz Baş Boyun Cerrahisi Hastalıkları Baş Boyun Cerrahisi Cildi içinde(s. 147-65) Ankara: Güneş Tıp Kitapevleri.
Stewart FA, Akleyev AV, Hauer-Jensen M, et al. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context. Ann ICRP. 2012; 41(1-2):1-322
Hur W, Yoon SK. Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells. International Journal of Molecular Sciences. 2017;18(12):2749
Sonis ST. Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncology, 2009;45(12):1015–20.
Kusiak A, Jereczek-Fossa BA, Cichońska D, et al. Therapy Related Oral Mucositis as an Interdisciplinary Problem-Literature Review. Int J Environ Res Public Health. 2020;17(7):2464.
Vera-Llonch M, Oster G, Hagiwara M, et al. Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma. Cancer. 2006;106(2):329-36.
Bhide SA, Gulliford S, Schick U, , et al. Dose–response analysis of acute oral mucositis and pharyngeal dysphagia in patients receiving induction chemotherapy followed by concomitant chemo-IMRT for head and neck cancer. Radiotherapy and Oncology. 2012;103(1):88–91
Nishii M, Soutome S, Kawakita A, et al. Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients. Supportive Care in Cancer. 2020;28(3):1069–75.
Mallick S, Benson R, Rath GK. Radiation induced oral mucositis: a review of current literature on prevention and management. European Archives of Oto-Rhino-Laryngology. 2016;273(9):2285–93.
Nanda SS, Gandhi AK, Rastogi M, et al. Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy. International Journal of Radiation Oncology Biology Physics. 2018;101(3):593–601.
Villa A, Vollemans M, De Moraes A, et al. Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers. Supportive Care in Cancer. 2021;29(10):6061–8.
World Health Organization (1979) WHO handbook for reporting results of cancer treatment. World Health Organization: Geneva
Department Of Health And Human Services(United States). Common Terminology Criteria for Adverse Events(CTCAE) Version5(https://search.nih.gov/search?utf8=%E2%9C%93&affiliate=nih&query=Common+Terminology+Criteria+for+Adverse+Events+%28CTCAE%29&commit=Search adresinden erişilmiştir)
Elad S, Cheng KKF, Lalla RV, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020;126(19):4423–31.
Mcguire DB, Fulton JS, Park J, et al. Systematic review of basic oral care for themanagement of oral mucositis in cancer patients. Support Care Cancer. 2013; 21(11):3165–77.
Bossi P, Numico G, De Santis V, et al. Prevention and treatment of oral mucositis in patients with head and neck cancer treated with (chemo) radiation: report of an Italian survey. Support Care Cancer 2014;22(7):1889–96
Vasin MV. Comments on the mechanisms of action of radiation protective agents: basis components and their polyvalence. SpringerPlus. 2014;3(1):414
Bensadoun R-J, Schubert MM, Lalla RV et al. Amifostine in the management of radiation-induced and chemo-induced mucositis. Supportive Care in Cancer. 2006;14(6):566–72
King M, Joseph S, Albert A, et al. Use of Amifostine for Cytoprotection during Radiation Therapy: A Review. Oncology. 2020;98(2):61-80
Rades D, Fehlauer F, Bajrovic A, Mahlmann B, Richter E, et al. Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients. Radiother Oncol. 2004; 70: 261–4.
Haddad R, Sonis S, Posner M, et al. Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/ paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer. Cancer. 2009;115:4514–23.
Cotrim AP, Yoshikawa M, Sunshine AN, et al. Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis. International Journal of Radiation Oncology Biology Physics. 2012;83(4):1284–90
Hu L, Wang Y, Cotrim A, Zhu Z, Gao R, Zheng C, et al. Effect of Tempol on the prevention of irradiation-induced mucositis in miniature pigs. Oral Diseases. Oral Diseases.2017;23(6):801–8
Blijlevens N, Sonis S May. Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy-and radiotherapy-induced mucositis. Ann Oncol. 2007;18 (5): 817-26.
Coutsouvelis J, Corallo C, Spencer A, et al. A meta-analysis of palifermin efficacy for the management of oral mucositis in patients with solid tumours and haematological malignancy. Critical Reviews in Oncology/Hematology. 2022;172:103606
Saunders DP, Rouleau T, Cheng K, et al. Systematic review of antimicrobials,mucosal coating agents, anesthetics, and analgesics for themanagement of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2020;28:2473-2484.
Legouté F, Bensadoun R-J, Seegers V, et al. Low-level laser therapy in treatment of chemoradiotherapy-induced mucositis in head and neck cancer: results of a randomised, triple blind, multicentre phase III trial.. Radiation Oncology. 2019;14(1)
Cronshaw M, Parker S, Anagnostaki E, et al. Photobiomodulation and Oral Mucositis: A Systematic Review. Dentistry Journal. 2020;8(3):87.
Agbele AT, Hejazi SM, Dehpour AR, et al. Treatment Parameters of Photobiomodulation in the Prevention of Non-surgical Cancer Treatment-Induced Oral Mucositis: A Review of Preclinical Studies. Journal of Lasers in Medical Sciences.2021;12(1):e54.
Lai C-C, Chen S-Y, Tu Y-K, et al. Effectiveness of low level laser therapy versus cryotherapy in cancer patients with oral mucositis: Systematic review and network meta-analysis. Critical Reviews in Oncology/Hematology. 2021;160:103276.
Münstedt K, Männle H. Using Bee Products for the Prevention and Treatment of Oral Mucositis Induced by Cancer Treatment. Molecules. 2019;24(17):3023.
Yarom N, Hovan A, Bossi P, et al. Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines-part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. Support Care Cancer. 2020;28:2457-72.
